that while the longer gene product Mcl-1L enhances cell survival by inhibiting apoptosis in response to various stress conditions in different cell types, the alternatively spliced shorter gene product Mcl-1S may promote apoptosis25,26. Hence, the possibility arises that alternative splicing of Mcl-1 may be involved in the mechanism involved in ethanol-induced neurotoxicity during the developmental period. In order to determine this, we investigated the potential impact of EtOH exposure on cellular toxicity and alternative splicing of Mcl-1 pre-mRNA and its involvement with cytotoxicity induced by EtOH in different lineages of neuronal cultures in an in vitro primary culture model where human neurospheres, neural progenitors, immature neurons, and mature neuron cultures were prepared and utilized from matching human fetal brain tissue. Our results suggest that human neurospheres, neural progenitors, and immature neurons but not the mature neurons are highly sensitive to the toxic effects of EtOH in a time and dose dependent manner. Interestingly, Mcl-1 missplicing leading to a decrease in Mcl-1L/Mcl-1S ratio is mainly observed in neural progenitors and immature neurons with no significant alteration in mature neurons. More interestingly, overexpression of antiapoptotic Mcl-1L isoform in neural progenitor cells is able to reverse the viability loss and apoptosis induced by
